When will triple-negative breast cancer produce landmark treatments?

Text | Drug Crazy

Breast cancer is the number one cancer in women, accounting for approximately 12% of all new cancer cases and 25% of all types of cancer in women.

1.

Molecular classification includes basal cell-like type 1 and 2, immunomodulatory type, mesenchymal stem cell-like type, mesenchymal type, and luminal androgen receptor type.

Currently, chemotherapy is still the main treatment method for TNBC, surgery is still the best method for local control of TNBC, and radiotherapy is also a treatment method for local control of TNBC and can reduce distant metastases caused by poor local control.

Figure 1.

Reference: Critical Reviews in Oncology / Hematology (2020)

2.

Neoadjuvant chemotherapy

TNBC greatly benefited from the first treatment.

Adjuvant chemotherapy

Combination therapy of anthracyclines and taxanes can not only reduce the adverse cardiac reactions of anthracyclines but also reduce the acquired resistance of taxanes.

3.

PARP inhibitors can not only increase the sensitivity of tumor cells to chemotherapeutic drugs, but also prevent PARP from repairing damaged DNA, and then promote the death of tumor cells in patients with BRCA1 mutations.

In a clinical trial for advanced breast cancer with BRCA1 and BRCA2 mutations, patients were randomly divided into a high-dose group (400 mg each time, twice a day) and a low-dose group (100 mg each time, each time 2 times a day), the results showed that the total remission rates of the two groups were 41% and 22%, respectively, showing the function of PARP monotherapy in the treatment of TNBC and BRCA1/2 mutation-related breast cancers.

Figure 3.

Reference: Pharmacology & Therapeutics (2019)

4.

PD-L1/PD-1 inhibitors are naturally also a hot spot related to TNBC research, especially PD-L1, although it is not a first-line drug recommendation in the guideline, it has also been included in the guideline.

TNBC has a higher expression of PD-L1, its expression level is related to tumor infiltrating lymphocytes and its receptor PD-1 is involved in the regulation of immune tolerance.
For example, the overall response rate of PD-1 antibody Pembrolizumab and PD-L1 antibody Atezolizumab in the treatment of TNBC is about 20%; a patient who is positive for PD-L1 in the advanced stage of TNBC was treated with PD-1 antibody Pembrolizumab, and the trial results showed a remission rate of 18.
5 % (5/27), the stability rate is 25.
9%.

The 2016 ASCO conference also reported the PD-L1 antibody Atezolizumab combined with albumin-bound paclitaxel in the treatment of TNBC clinical trials that have not exceeded the third-line treatment.
The median follow-up was 5.
21 months.
The results showed that the overall response rate was 71%.
The most common treatment-related adverse reaction is neutropenia.
This is the first time that immunotherapy and chemotherapy have been combined to verify the therapeutic effect of TNBC, which is of great significance and proves that the combination of the two can greatly improve the efficacy of TNBC.

Figure 4.
1 NCCN's recommendation for PD-L1 inhibitors

Reference: NCCN Guidelines Version 1.
2021 Breast Cancer

5.
Summary

In summary, it is the current status of TNBC in drug treatment.
Chemotherapy drugs are still the first-line drugs for clinical treatment, and their special pathological characteristics greatly limit the feasibility of targeted therapy.
PD-1/PD-L1 inhibitors have begun to show certain effects.
However, TNBC has not yet received a breakthrough treatment, and clinical needs and clinical problems need to be solved urgently.
The indication market is worth the heavy investment of drug research and development companies.
Generally speaking, the future can be expected.

Reference materials:

1.
Critical Reviews in Oncology / Hematology (2020).
https://doi.
org/10.
1016/j.
pharmthera.
2019.
02.
006

2.
NCCN Clinical Practice Guidelines in Oncology (NCCN) 2021.

3.
COSO Breast Cancer 2020.